Several reasons why ketamine as a neuroplastic agent may have failed to prevent postoperative delirium: Implications...

Area of Science:

• Anesthesiology and Perioperative Medicine
• Neuroscience and Neuropharmacology
• Critical Care and Emergency Medicine

Background:

• Postoperative delirium (POD) is a common complication associated with significant morbidity and mortality.
• Ketamine exhibits anti-inflammatory, neuroprotective, and neuroplastic properties that theoretically could mitigate POD.
• Previous clinical studies investigating ketamine for POD prevention have largely failed to demonstrate efficacy.

Purpose of the Study:

• To identify pharmacological reasons for the failure of prior ketamine studies in POD prevention.
• To propose strategies to optimize ketamine administration for preventing POD.
• To suggest biomarkers for assessing ketamine's impact on neuroplastic pathways relevant to POD.

Main Methods:

• Pharmacological analysis of ketamine's mechanism of action, particularly its interaction with GABAergic systems.
• Review of existing literature on ketamine, general anesthetics, and their effects on neuroplasticity.
• Hypothesizing optimal timing for ketamine administration relative to general anesthesia and surgery.

Main Results:

• A key identified pitfall is the antagonistic interaction between ketamine and intravenous general anesthetics on GABA interneurons.
• This interaction may counteract ketamine's beneficial neuroprotective and neuroplastic effects.
• Proposed biomarkers could elucidate the influence of this interaction on neuroplasticity.

Conclusions:

• Administering ketamine before or after general anesthesia, rather than during, may prevent detrimental interactions.
• Strategic timing could enhance ketamine's neuroplastic effects, potentially by stabilizing AMPA receptors.
• Current study protocols using ketamine during general anesthesia need re-evaluation due to this identified pitfall.